s0008: chemotherapy plus biological therapy in treating patients with melanoma

Conditions: Melanoma (Skin)

Summary: rationale: interferon alfa may interfere with the growth of cancer cells. drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. it is not yet known whether interferon alfa is more effective with or without combination chemotherapy and interleukin-2 for melanoma. purpose: randomized phase iii trial to compare the effectiveness of interferon alfa with or without combination chemotherapy consisting of cisplatin, vinblastine, and dacarbazine, plus interleukin-2, in treating patients who have melanoma.

objectives: * compare the overall survival and disease-free survival of patients with high-risk melanoma treated with interferon alfa vs cisplatin, vinblastine, and dacarbazine plus interferon alfa and interleukin-2. * compare the toxic effects of these treatment regimens in these patients. * determine the relationship between minimal residual disease (mrd) status at 12 weeks and 52 weeks and overall survival of patients treated with these regimens. * compare the effects of these treatment regimens on the mrd status of these patients. * determine the relationship between clinical characteristics (number of involved lymph nodes, ulcerated primary, and extracapsular extension) and mrd in patients treated with these regimens. outline: this is a randomized, multicenter study. patients are stratified according to nodal status (n1 or n2 vs n3), degree of lymph node involvement (micrometastases only vs any macrometastases, including satellite/in-transit metastases), and ulceration of the primary tumor (yes vs no vs unknown primary). patients are randomized to 1 of 2 treatment arms. * arm i: patients receive interferon alfa iv on days 1-5 of weeks 1-4 followed by interferon alfa subcutaneously (sc) on days 1, 3, and 5 of weeks 5-52 in the absence of disease progression or unacceptable toxicity. * arm ii: patients receive cisplatin iv over 30 minutes followed by vinblastine iv on days 1-4. patients also receive dacarbazine iv over 1 hour on day 1, interleukin-2 iv over 96 hours on days 1-4, and interferon alfa sc on days 1-5, 8, 10, and 12. in addition, patients receive filgrastim (g-csf) sc on days 6-15. treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years. projected accrual: a total of 410 patients (205 per treatment arm) will be accrued for this study within 3 years.

Eligibility criteria:
disease characteristics: * histologically proven melanoma of cutaneous origin or from unknown primary at initial presentation of primary or first clinically detected nodal or satellite/in-transit recurrence * no distant metastases * no melanoma of ocular, mucosal, or other non-cutaneous origin * one of the following criteria must apply for patients with newly diagnosed melanoma or a previously diagnosed primary with current subsequent, clinical, regional nodal disease and/or satellite/in-transit disease: * ulcerated primary melanoma with 1 or more involved lymph nodes (micro/occult or macro/clinically overt) * non-ulcerated or unknown primary melanoma with one macro/clinically overt lymph node metastasis, including a single matted nodal mass * no non-ulcerated or unknown primary tumor and a single micrometastatic lymph node * non-ulcerated melanoma with two or more lymph node metastases (micro/occult or macro/clinically overt) and/or matted nodes * any satellite/in transit metastasis with or without lymph node involvement * patients with recurrent disease must have recurrent disease in the regional nodal basin of a prior complete lymphadenectomy * multiple regional nodal basin involvement allowed if they are appropriate anatomic drainage basins for primary site * patients must be disease free at time of enrollment based on the following surgical criteria: * patients at initial presentation of melanoma must undergo adequate wide excision of primary lesion * patients with previously diagnosed melanoma must have all disease resected with pathologically negative margins and no disease at primary site or second resection of primary * full lymphadenectomy required of all patients including those with positive sentinel nodes or positive satellite/in-transit metastasis * no more than 56 days since prior lymphadenectomy or surgery to remove recurrent disease after prior complete lymphadenectomy * must be willing to participate in minimal residual disease studies if registered on the study on 3/1/2003 or later patient characteristics: age: * 18 and over performance status: * zubrod 0-1 life expectancy: * not specified hematopoietic: * absolute granulocyte count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 1.5 times upper limit of normal (uln) * sgot or sgpt no greater than 2 times uln * ldh and alkaline phosphatase no greater than 2 times uln (above normal value requires a contrast-enhanced ct scan or mri of liver) * no known recent hepatitis positivity by pcr renal: * creatinine no greater than 1.5 mg/dl or * creatinine clearance at least 75 ml/min cardiovascular: * no congestive heart failure * no coronary artery disease * no serious cardiac arrhythmia * no prior myocardial infarction * normal cardiac stress test required if any of the following are present: * over age 50 * abnormal ekg * history of cardiac disease pulmonary: * no symptomatic pulmonary disease other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no autoimmune disorders or conditions of immunosuppression * no other prior malignancy within the past 5 years except the following: * adequately treated basal cell or squamous cell skin cancer * carcinoma in situ of the cervix * adequately treated stage i or ii cancer in remission * hiv negative * no known aids or hiv-1 associated complex prior concurrent therapy: biologic therapy: * no prior immunotherapy, including interferon, interleukin, levamisole, or other biologic response modifiers * no other concurrent biologic therapy chemotherapy: * no prior chemotherapy (including infusion or perfusion therapy) * no other concurrent chemotherapy endocrine therapy: * no concurrent systemic corticosteroids or topical steroid creams * concurrent steroid antihistamines allowed if no alternative * no concurrent hormonal therapy radiotherapy: * no prior radiotherapy * prior postlumpectomy radiotherapy for breast cancer allowed * no concurrent radiotherapy surgery: * see disease characteristics * no concurrent surgery other: * no concurrent anti-hypertensive medications (arm ii only) * no concurrent immunosuppressive agents * no other concurrent anticancer therapy * antihistamines allowed if no alternative medication suitable

Keywords: stage iii melanoma recurrent melanoma